Chemical Properties
White Powder
Uses
2-Chloro-4,6-dimethoxypyrimidine is used as building block in chemical synthesis. Product Data Sheet
Uses
2-Chloro-4,6-dimethoxypyrimidine is a useful reactant for the synthesis of polycyclic fused and spiro-4-aminopyridines
Synthesis
General procedure for the synthesis of 2-chloro-4,6-dimethoxypyrimidine from 2-amino-4,6-dimethoxypyrimidine:
1. 1,260 ml of 36% hydrochloric acid was added to a 5-liter four-necked flask and subsequently cooled to 0°C.
2. 180 g (1.16 moles) of 2-amino-4,6-dimethoxypyrimidine was added to the flask in batches and stirred continuously for about 1 hour until the reaction mixture took on a syrupy consistency.
3. After the reaction mixture was further cooled to -15°C, 260 ml of an aqueous solution containing 159 g (2.3 moles) of NaNO2 was slowly added dropwise over a period of about 1 hour under vigorous stirring.
4. after completion of the dropwise addition, the mixture was continued to be stirred at -15°C to -10°C for 1 hour to ensure complete reaction.
5. While keeping the reaction mixture at -5°C, 1.5 liters of 30% aqueous NaOH was slowly added dropwise to adjust the pH to 7 for neutralization.
6. The resulting purple clay-like substance was collected by filtration under reduced pressure.
7. the target compound 2-chloro-4,6-dimethoxypyrimidine was extracted from the clay-like material using 3 liters of ethyl acetate.
8. The organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was removed to yield 63 g of light blue crude crystals.
9. Purification and crystallization by silica gel chromatography resulted in 60.8 g of white crystals (yield: 29.9%) with a melting point of 101.5°-102.5°C. The final product was purified by silica gel chromatography.
References
[1] Patent: US4986846, 1991, A
[2] Pesticide Science, 1996, vol. 47, # 2, p. 103 - 114
